Fistula (pl. fistulas or fistulae) is an abnormal connection or passageway between organs or vessels that normally do not connect. Fistulas can develop in various parts of the body in connection with diseases in the circulatory-, respiratory-, digestive-, genitourinary-, musculoskeletal systems and connective tissue beside congenital malformations, deformations and chromosomal abnormalities.
The type of the fistula can be blind with only one open end, it can be complete with both an external and a internal opening or incomplete with a external skin opening, which does not connect to any internal organs. The most common form of fistulas is in forms of a tube with the possibility to have multiple branches.
Treatment for fistula varies dependent on the cause and extent of the fistula, but often involves surgical intervention combined with antibiotic therapy. Treatments involving filling the fistula with fibrin glue or plugging it with plugs made of SIS have also been explored in recent years.
Scaffolds are structures used to guide the organization, growth and differentiation of cells in the process of forming new functional tissue.
To achieve the goal of tissue reconstruction, scaffolds must meet some specific requirements. A high porosity and an adequate pore size are necessary to facilitate cell growth and diffusion throughout the whole structure of both cells and nutrients.
Biodegradability is essential since scaffolds need to be absorbed by the surrounding tissues without the necessity of a surgical removal.
Many different materials (natural and synthetic, biodegradable and permanent) have been investigated for use as scaffolds. Most of these materials have been known in the medical field before the advent of tissue engineering as a research topic, being already employed as bioresorbable sutures. Examples of these materials are collagen or some linear aliphatic polyesters.
However, when testing laboratory made scaffolds in vivo, it is often seen, that the cells do not grow readily into these scaffolds, maybe due to the fact that no biological signal molecules, e.g. growth factors, are found in synthetically made scaffolds.
In order to improve the biological properties of the scaffolds and to accelerate wound healing, several labs have added growth factors to a synthetic scaffold and seen beneficial effects on wound healing. In all of these publications a single growth factor has been incorporated in a sheet or hydrogel. The growth factors examined have been FGF-2 (1; 2), β-FGF-2 tested in a concentration of 25 μg/cm2 (2), FGF-1 (3; 4), EGF (5)(14), or TGF-β (6; 7) in a concentration of 2 μg/cm2. Acellular extracellular matrices (ECM) from warm-blooded vertebras are used extensively in tissue engineering and plastic surgery (8). It has been shown that acellular ECM contains several growth factors (9-11). ECMs contain a lot of biologic molecules and it has been shown that cells readily populate these sheets of concentrated ECM (12; 13). The ECMs on the market today are of human or porcine origin. The cells are removed from the tissue and the tissue is subsequently lyophilized and cut into sheets. The sheets of porcine origin come in different sizes. The price of these sheets is very high. The sheets are fairly stiff when un-hydrated. An example is the sheets from the company Acell. They sell sheets of ECM (Urinary Bladder Matrix, UBM) that accelerate the wound healing. Such sheet (7×5 cm) weighs about 100 mg and has a density of about 190 mg/cm3.
Use of ECMs or ECM proteins for healing and regeneration of wounds is known. These products are in the form of sheets or hydrogels. Examples of sheet products are OASIS from Healthpoint (lyophilized porcine ECM sheet) and Graftjacket from Wright medical (lyophilized human ECM sheet). The sheets provide both a scaffold as well as a complex mixture of proteins to the cells of the wound. Examples of non-scaffold products containing ECM proteins on the market, is Xelma from Molnlycke, which is a hydrogel that contains a protein extract from ECM of developing pig teeth. Cook provides Surgisis® AFP™ Anal Fistula Plug for the treatment of anal fistulas. A plug made of ECM sheet.